The overall objectives of this project are to conduct Phase I and II clinical trials of black cohosh (Cimicifuga racemosa) and red clover (Trifolium pratense), to be used for women's health problems-for menopausal hot flashes (primarily) and other somatic symptoms. Observational and epidemiological studies demonstrated that black cohosh is effective for menopausal women, and safe (at least in short-term). Phase I:
The aims of this study is to determine safe doses (acute toxicity) of extracts of both botanicals, to be used in the subsequent Phase II clinical trial. Three doses will be tested over a one-week period in an attempt to determine symptoms of acute toxicity. There will be 5 subjects for each of 3 dosages (1X, 2X, 3X) of the 2 botanicals. (N=30) The goal is a sample size large enough to estimate unknown parameters Also studied will be pharmacokinetics (hourly bloods) absorption, distribution, metabolism, elimination, and pharmacological mode of action and side effects in healthy menopausal women. Phase II: This is a one year, randomized, controlled, double-blind efficacy study, the primary aim of which is to evaluate the efficacy of black cohosh and red clover, over a """"""""safe dose range,"""""""" for menopausal hot flashes. Additional goals are to assess these botanicals for other menopausal symptoms such as insomnia, joint pain, vaginal dryness, and dyspareunia (using Kupperman Index, bleeding scales and index of sexual function). They will also assess longer-term risks and safety issues and to determine changes in biomarkers (such as bone turnover and lipids) associated with use of these botanicals. Most previous studies of black cohosh lasted at most 6 months. Longer-term (1-year) safety data will be evaluated. In particular, incidence of endometrial hyperplasia, breakthrough bleeding, and other side effects will be determined. Subjects (n=112) will be randomized into one of 4 treatment groups (28/gr): placebo, Prempro 0.625/2.5, black cohosh and red clover. Also they will take blood samples to measure DNA oxidation products for measurements of DNA strand breaks using the comet assay to determine if DNA in peripheral blood leukocytes is being protected from damage through the antioxidant properties of the 'active' compounds or whether DNA damage is being produced (indicator of toxicity).
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